ClinVar Miner

Submissions for variant NM_015001.3(SPEN):c.4345G>T (p.Glu1449Ter)

dbSNP: rs2148739431
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine RCV001733859 SCV001983779 pathogenic Radio-Tartaglia syndrome 2021-10-27 no assertion criteria provided clinical testing This variant is absent from the gnomAD database. The probability of loss-of-function intolerance (pLI) of this gene is 1 in the gnomAD browser, which suggests that SPEN is highly intolerant to heterozygous loss-of-function variants. SPEN is also reported to be enriched in de novo and truncating variants in patients with a developmental disorder (Wang et al. 2020; Radio et al. 2021). It encodes a transcriptional repressor with a major role in the initiation of X chromosome inactivation (Dossin et al. 2020). Pathogenic variations in SPEN have been very recently associated with a neurodevelopmental disease in two clinical cohorts (Wang et al. 2020; Radio et al. 2021). The patient's phenotype appears to be consistent with the descriptions in the literature.

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